Genetic factors associated with rheumatoid arthritis and systemic vasculitis: Evaluation of a panel of polymorphisms

Immune and inflammatory response activation is a common feature of connective tissue diseases and systemic vasculitis. The aim of our study was to evaluate the possible involvement of TNF alpha c.-308A > G, IL-10 c.-1082A > G, uteroglobin c. 38A > G, TGF beta 1 c. 869C > T and NF kappa B2 c.-1837T > C gene polymorphisms in susceptibility to connective tissue diseases. Our study cohort included 68 unrelated patients affected by rheumatoid arthritis (RA) (37 patients) and ANCA-positive [micropolyangiitis (mPA) 17 patients] or ANCA-negative systemic vasculitis [including 8 patients with Henoch-Schonlein purpura (HSP) and 6 patients with mixed cryoglobulinaemia (MC)] as well as 98 control subjects. Allele frequency analysis of uteroglobin c. 38G > A polymorphism showed a significant increase in the c. 38A allele in patients (p = 0.002). Genotype frequency analysis of uteroglobin and NF-kappa B2 gene polymorphisms in patients showed an increase in c. 38GA and c. 38AA genotypes in the uteroglobin gene (p = 0.02) coupled with an increase in homozygous c.-1837CC in the NF-kappa B2 gene (p = 0.02). Our data suggest that genetic variation in UG and NF-kappa B2 pathways could have effects in connective tissue disease susceptibility.